Large neutral amino acid transporter 1 (LAT1, SLC7A5) is abundantly expressed in various types of cancer, and it has been thought to assist cancer progression through its activity for uptake of neutral amino acids. However, the roles of LAT1 in renal cell carcinoma (RCC) prognosis and treatment remain uncharacterized. Therefore, we first retrospectively examined the LAT1 expression profile and its associations with clinical factors in RCC tissues (n = 92). The results of immunohistochemistry showed that most of the tissues examined (92%) had cancer-associated LAT1 expression. Furthermore, the overall survival (OS) and progression-free survival (PFS) were shorter in patients with high LAT1 expression levels than in those with low LAT1 expression levels (P = 0.018 and 0.014, respectively), and these associations were further strengthened by the results of univariate and multivariate analyses. Next, we tested the effects of JPH203, which is a selective LAT1 inhibitor, on RCC-derived Caki-1 and ACHN cells. It was found that JPH203 inhibited the growth of these cell types in a dose-dependent manner. Moreover, JPH203 clearly suppressed their migration and invasion activities. Thus, our results show that LAT1 has a great potential to become not only a prognosis biomarker but also a therapeutic target in RCC clinical settings.
Scientific reports. 2019 Nov 20*** epublish ***
Kosuke Higuchi, Shinichi Sakamoto, Keisuke Ando, Maihulan Maimaiti, Nobushige Takeshita, Kentaro Okunushi, Yoshie Reien, Yusuke Imamura, Tomokazu Sazuka, Kazuyoshi Nakamura, Jun Matsushima, Tomomi Furihata, Yuzuru Ikehara, Tomohiko Ichikawa, Naohiko Anzai
Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Pathology, Dokkyo Medical University Saitama medical center, Saitama, Japan., Department of Clinical Pharmacy and Experimental Therapeutics, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan., Department of Molecular Tumor Pathology, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan. .